Distinct subnetworks of the thalamic reticular nucleus

The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition . TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple ne...

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Published inNature (London) Vol. 583; no. 7818; pp. 819 - 824
Main Authors Li, Yinqing, Lopez-Huerta, Violeta G, Adiconis, Xian, Levandowski, Kirsten, Choi, Soonwook, Simmons, Sean K, Arias-Garcia, Mario A, Guo, Baolin, Yao, Annie Y, Blosser, Timothy R, Wimmer, Ralf D, Aida, Tomomi, Atamian, Alexander, Naik, Tina, Sun, Xuyun, Bi, Dasheng, Malhotra, Diya, Hession, Cynthia C, Shema, Reut, Gomes, Marcos, Li, Taibo, Hwang, Eunjin, Krol, Alexandra, Kowalczyk, Monika, Peça, João, Pan, Gang, Halassa, Michael M, Levin, Joshua Z, Fu, Zhanyan, Feng, Guoping
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 30.07.2020
Subjects
Animals
Attention
Cluster Analysis
Divergence
Female
Functional morphology
Gene expression
Gene Expression Profiling
Gene Regulatory Networks
Heterogeneity
In Situ Hybridization, Fluorescence
In vivo methods and tests
Information processing
Metalloendopeptidases - metabolism
Mice
Neural networks
Neural Pathways
Neurodevelopmental disorders
Neurons
Neurons - metabolism
Osteopontin - metabolism
Patch-Clamp Techniques
Perturbation
RNA-Seq
Sensory integration
Sensory perception
Single-Cell Analysis
Sleep
Sleep - genetics
Sleep - physiology
Subpopulations
Thalamic nuclei
Thalamic Nuclei - cytology
Thalamic Nuclei - metabolism
Thalamic Nuclei - physiology
Thalamic reticular nucleus
Thalamus
Transcriptome
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Summary:The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition . TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders . However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits.
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These authors jointly supervised this work.
These authors contributed equally.
Y.L., V.G.L.H., J.Z.L., Z.F. and G.F. provided overall design and oversight of the project. snRNA-Seq experiments were designed, performed, analyzed, or supervised by Y.L., V.G.L.H., X.A., C.H., S.K.S., and T.L. A modified protocol for Smart-seq2 library construction was contributed by M.K. Viral injections and collection of non-TRN Pvalb+ neuronal nuclei was performed by R.S. and V.G.L.H. RNA FISH experiments were designed, performed, analyzed, or supervised by Y.L., K.L., A.Y.Y., T.R.B., A.A., M.G. and J.P. EEG recording and analyses were designed and performed by S.C., R.D.W, V.G.L.H., T.N., X.S., D.B., E.H., G.P., and M.M.H. Electrophysiology, Patch-Seq and morphology experiments were designed, performed, analyzed, or supervised by V.G.L.H., M.A.A.G., Y.L., and Z.F. Retrograde tracing experiments were performed by V.G.L.H., Y.L., A.Y.Y., A.A., K.L. and A.K. CRISPR knockout experiments were designed and performed by Y.L., V.G.L.H., X.A., T.A., A.Y.Y., A.A., D.M. The manuscript was written by Y.L., V.G.L.H., Z.F., G.F., J.Z.L., and M.M.H. with inputs from all authors. J.Z.L, Z.F., and G.F. contributed equally to the joint supervision of the work.
Author contributions
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-020-2504-5